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HELLO! This message came to me today via email. Too bad the photo of Drs. Rugo and Winer is not there.

Consensus or Controversy: Lincoln-Sudbury High grads Eric and Hope comment on HER2-positive metastatic breast cancer

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One of my favorite moments during our recent 4-city Year in Review (YIR) CME tour occurred in New York when GI investigator Dr Alan Venook revealed a little-known fact — namely that the prior 2 speakers participating in the breast cancer module, Drs Hope Rugo and Eric Winer, went to high school together. I later learned that the academic institution these noted investigators attended was Lincoln-Sudbury Regional High School outside of Boston and that Eric — who was a year ahead — knew Hope through her brother, who was his classmate. An avid cyclist, Eric still regularly rides his bike past the house where Hope grew up.

Dr Venook, who had been listening in on the meeting before taking the stage, commented on the “spirited interplay” he observed between the 2 former Lincoln-Sudbury Warriors, which from our perspective made for edu-tainment at its finest. So much so that for this issue of Consensus or Controversy we attempt to recreate that dynamic for those of you who were not there by comparing the perspectives of these former classmates to those of the CoC faculty that included Hope. The topic is the most dynamic current corner of solid tumor oncology — management of HER2-positive metastatic breast cancer (HER2+ mBC). Here are the major questions addressed:

1. What are the current standard first- and second-line anti-HER2 treatments for HER2+ mBC?
Over the past 18 months, clinical treatment for these patients has undergone an unprecedented, dramatic and rapid transformation. First, the CLEOPATRA study evaluating a taxane (docetaxel), trastuzumab and pertuzumab (THP) demonstrated a remarkable 6-month prolongation of progression-free survival with a 0.62 hazard ratio, a survival advantage and minimal additional toxicity. As a result, THP instantly became standard treatment first line in the investigator community. However, a more gradual adoption of this approach occurred in general oncology practice, and even as recently as 6 months ago postactivity evaluations conducted after our live CME meetings revealed that a significant fraction of audience members walked out of the room with a new clinical algorithm.

In that same vein, the EMILIA trial cemented ado-trastuzumab emtansine (T-DM1) as the unquestioned second-line treatment among investigators when it was approved in February 2013, but the widespread adoption of this fascinating antibody-drug conjugate as second-line therapy continues.

In discussing this paradigm shift Hope and Eric referred to an upcoming ASCO guideline that will include discussion of the critical issue of sequencing the many current options available for these patients. However, 100% of the CoC faculty agree with the primary algorithm of THP followed by T-DM1.

2. What is the optimal initial systemic treatment for a patient with ER-positive/HER2-positive metastatic disease?
Like many friends, Drs Rugo and Winer don’t always agree, and during our YIR meeting the two made no attempt to hide their different approaches to these patients with challenging “double-positive” disease. Hope finds the CLEOPATRA benefit quite compelling and virtually always starts with this strategy, pointing out that the commitment to chemotherapy (with pertuzumab and trastuzumab) is limited (for her, 6 cycles) and patients can then be followed on both antibodies and an endocrine treatment.

Eric has no problem with Hope’s approach, particularly for symptomatic patients, but he more often combines a hormone with anti-HER2 treatment — for now trastuzumab but maybe in the future also pertuzumab if benefit is observed in the ongoing randomized Phase II PERTAIN trial that compares trastuzumab with an aromatase inhibitor alone or with pertuzumab.

Both of these sentiments are reflected in the CoC investigator comments (which are well worth the read). However, visceral involvement and the presence of symptoms push many more to THP, and all will go to that strategy first in symptomatic patients with visceral metastases.

3. Two practical issues
• Is it reasonable to combine pertuzumab and T-DM1 outside a protocol setting?
Like virtually all breast cancer clinical investigators, Drs Rugo and Winer agree that the temptation to try this provocative approach should be completely resisted for the simple reason that we lack sufficient safety or efficacy data.

• Is it reasonable to utilize pertuzumab in later lines of treatment than the current indication of first line?
There is also consensus that later-line therapy is likely to provide benefit and that the only obstacle to allowing any patient with HER2+ mBC to access this therapy at least once relates to regulatory or reimbursement issues.

It should be duly noted that neither Hope nor Eric is identified as a notable Lincoln-Sudbury alumnus on the school’s website, but as always they will be among the most visible leaders next week during the annual San Antonio spectacular. In this regard, Eric’s team will be reporting on the adjuvant trastuzumab/paclitaxel trial in node-negative HER2-positive disease and Hope will unveil an I-SPY2 TRIAL (Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging And moLecular Analysis 2) neoadjuvant data set.

And if you find yourself in the city by the river Wednesday night, sign up for our annual CME satellite adventure where these and other compelling issues of the day will be discussed and debated.

Neil Love, MD
Research To Practice
Miami, Florida

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This activity is supported by educational grants from Genentech BioOncology, Genomic Health Inc and Novartis Pharmaceuticals Corporation.

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